Submitted on February 23, 2008
Revised on February 13, 2009
Accepted on February 16, 2009
Breakdown of endocytosis in the oncogenic activation of receptor tyrosine kinases
Jasmine Vanessa Abella1 and Morag Park1*
1 McGill University
* To whom correspondence should be addressed. E-mail: morag.park{at}mcgill.ca.
There is increasing evidence to support the concept that the malignant behavior of many tumors is sustained by the deregulated activation of growth factor receptors. Activation of receptor tyrosine kinases (RTKs) by their respective ligand(s) initiates cellular signals which tightly modulate cell proliferation, survival, differentiation and migration to ensure normal tissue patterning. Uncontrolled activation of such signals can therefore have deleterious effects leading to oncogenesis. To date, deregulation of most RTKs have been implicated in the development of cancer although the mechanisms which lead to their deregulation are not yet fully understood (10). RTK endocytosis, the internalization and trafficking of receptors inside the cell, has long been established as a mechanism to attenuate RTK signaling. However, RTKs have been demonstrated that to continue to signal along the endocytic pathway, which contributes to the spatio-temporal regulation of signal transduction. This review will focus on recent advances linking defective endocytosis of RTKs in the development of cancer.
